Mutational spectrum of GNAL, THAP1 and TOR1A genes in isolated dystonia: study in a population from Spain and systematic literature review

[Objective] We aimed to investigate the prevalence of TOR1A, GNAL and THAP1 variants as the cause of dystonia in a cohort of Spanish patients with isolated dystonia and in the literature.[Methods] A population of 2028 subjects (including 1053 patients with different subtypes of isolated dystonia and 975 healthy controls) from southern and central Spain was included. The genes TOR1A, THAP1 and GNAL were screened using a combination of high-resolution melting analysis and direct DNA resequencing. In addition, an extensive literature search to identify original articles (published before 10 August 2020) reporting mutations in TOR1A, THAP1 or GNAL associated to dystonia was performed.[Results] Pathogenic or likely pathogenic variants in TOR1A, THAP1 and GNAL were identified in 0.48%, 0.57% and 0.29% of our patients, respectively. Five patients carried the variation p.Glu303del in TOR1A. A very rare variant in GNAL (p.Ser238Asn) was found as a putative risk factor for dystonia. In the literature, variations in TOR1A, THAP1 and GNAL accounted for about 6%, 1.8% and 1.1% of published dystonia patients, respectively.[Conclusions] There is a different genetic contribution to dystonia of these three genes in our patients (about 1.3% of patients) and in the literature (about 3.6% of patients), probably due the high proportion of adult-onset cases in our cohort. As regards age at onset, site of dystonia onset, and final distribution, in our population there is a clear differentiation between DYT-TOR1A and DYT-GNAL, with DYT-THAP1 likely to be an intermediate phenotype.This work was supported by the Carlos III Health Institute-European Regional Development Fund (ISCIII-FEDER) [PI14/01823, PI16/01575, PI18/01898, PI19/01576], the Andalusian Regional Ministry of Economics, Innovation, Science and Employment [CVI-02526, CTS-7685], the Andalusian Regional Ministry of Health and Welfare [PI-0741-2010, PI-0471-2013, PE-0210-2018, PI-0459-2018, PE-0186-2019], and the Alicia Koplowitz and Mutua Madrileña Foundations. Pilar Gómez-Garre was supported by the "Miguel Servet" program [MSII14/00018] (from ISCIII-FEDER) and “Nicolás Monardes” program [C-0048-2017] (from the Andalusian Regional Ministry of Health). Silvia Jesús was supported by the "Juan Rodés" program [B-0007-2019] and Daniel Macías-García by the “Río Hortega” program [CM18/00142] (both from ISCIII-FEDER). María Teresa Periñán was supported by the Spanish Ministry of Education [FPU16/05061]. Cristina Tejera was supported by VPPI-US from the University of Seville.Peer reviewe

Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/

Intervención educativa para el manejo del dolor en personal de enfermería

Pain is currently considered as the fifth vital sign. The objective of the study was to determine the effectiveness of an educational program for nurses on pain management for patients with chronic degenerative and surgical problems. The employed method was a pre-experimental design with a pre-test and a posttest. The research population was made up of 42 nurses from two secondary health care institutions in the public sector. The Nurse’s Knowledge and Attitudes Survey Regarding Pain was used. Results showed that the pre-test mean knowledge of correct answers was 50.9 (SD = 9.65), with a minimum value of 28.1 and a máximum value of 78.1. The post-test mean was 70.4 (SD = 10.9) with a minimum value of 40.6 and a maximum value of 90.6. After the educational intervention, nurses demonstrated an increased level of knowledge regarding pain management (t (41) = -12.98; P < 0.001). The educational intervention study for nurses was effective in improving their knowledge regarding pain management in patients, since the participating nurses provided better attention and care after the educational intervention. This, however, was insufficient for most of the participating personnel.En la actualidad, el dolor es considerado como el quinto signo vital. El objetivo del trabajo fue determinar la efectividad de un programa educativo para el personal de enfermería sobre manejo de dolor en pacientes con problemas crónicos degenerativos y quirúrgicos. El método usado fue el diseño pre-experimental con pretest-postest. La población de estudio estuvo integrada por personal de enfermería (42) de dos instituciones de salud de segundo nivel de atención, del sector público. Se utilizó el cuestionario Conocimiento y Actitudes Respecto al Dolor. La media de respuestas correctas del conocimiento pretest fue de 50.9 (DE = 9.65), valor mínimo de 28.1 y máximo 78.1; y en el postest la media fue de 70.4 (DE = 10.9) valor mínimo de 40.6 y máximo 90.6. Posterior a la intervención educativa, se encontró mayor conocimiento en el personal de enfermería (t (41)= - 12.98; P < 0.001). El estudio de intervención educativa del personal de enfermería fue efectivo para mejorar el conocimiento sobre el manejo del dolor en los pacientes, ya que los primeros brindaron una mejor atención y cuidados, posteriores a la intervención educativa, no obstante, este fue insuficiente para la mayoría del personal participante.

Recomendaciones para el cuidado del cordón umbilical en el recién nacido.

The care of the umbilical cord until its detachment still remains controversial. The latest updated recommendations by the World Health Organisation advocate dry cord care in those countries with adequate obstetric care and low neonatal mortality rate. In recent years, new studies and reviews attribute some benefit to applying chlorhexidine on the umbilical stump. An analysis is presented here of the available evidence and results in the advisability of still recommending the dry cord care in the newborns in our setting

Proyecto de prevención de drogodependencias

Trata el problema de las drogodependencias desde el punto de vista de la prevención en el ámbito escolar y familiar. Estudia el contexto del centro, los factores de riesgo y los objetivos generales de etapa para Secundaria. Incluye los resultados de una encuesta sobre el consumo de alcohol y tabaco a alumnos de tercero y cuarto de ESO. Ofrece cinco unidades didácticas sobre alcohol, tabaco y publicidad, nueve sesiones de tutoría y actividades en el huerto escolar.Madrid (Comunidad Autónoma). Consejería de Educación y Cultura. Ministerio de Educación y Cultura. Ayuntamiento de MadridMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES

New models towards assessing anti-cancer therapeutics

Cancer is the subject of intense research around the world, but many questions about how the disease works remain unanswered. How exactly does cancer start and how do tumours grow? In fact, at present there are ten times more anticancer drugs being tested in clinical trials than there were 15 years ago. However, many of the new anticancer agents are predicted to show clinical benefit in only small subpopulations of patients. The cancer stem cell model could explain not only how some cancers work but also why patients suffer relapses, providing a good opportunity to gain insight into the reasons why agents work or, more commonly, don’t work, before going into a clinical tria